高强度聚焦超声联合微泡损伤山羊肝的增效性研究

目的 探讨超声造影剂SonoVue用于增强高强度聚焦超声(HIFU)损伤山羊肝组织的可行性.方法 南江黄羊15只,采用自身对照,分为HIFU治疗组(对照组)和HIFU联合造影剂治疗组(实验组).治疗深度30 mm,分别在声功率为150 W、250 W、350 W条件下对肝定点辐照15 S.辐照后24 h处死动物,解剖观察凝固性坏死情况,并作病理切片分析.结果 在相同声辐照参数下,实验组凝固性坏死发生率及凝固性坏死区域长、宽、厚、体积均明显大于对照组(P＜0.05),随功率增加实验组凝固性坏死体积增加幅度较对照组更明显,实验组能效因子(EEF)明显小于对照组.凝固性坏死区与正常肝组织分界清楚,且病理切片显示损伤为不可逆性,分界处可见大量空泡.结论 HIFU联合微泡造影剂能在山羊肝中形成完全的凝固性坏死,同时提高凝固性坏死的损伤率,增大凝固性坏死体积,提高HIFU治疗效率.     

The ABCs of asthma control

The new asthma guidelines have introduced impairment and risk assessments into the management of asthma. Impairment assessment is based on symptom frequency and pulmonary function, whereas risk assessment is based on exacerbation frequency and severity. These 2 measures determine the initial severity of asthma in the untreated patient as well as the degree of control in asthma once treatment has been initiated. The focus on asthma control is important because the attainment of control correlates with a better quality of life and reduction in health care use. We describe 4 easy steps to achieving asthma control in the ambulatory practice setting: (1) a standardized assessment of asthma symptoms using a 5-question assessment tool called the Asthma Control Test, (2) a simple mnemonic that provides a systematic review of the comorbidities and clinical variables that contribute to uncontrolled asthma, (3) directed patient education, and (4) a schedule for ongoing care. Most if not all patients can achieve good control of their asthma with optimal care through an active partnership with their health care professionals.     

静脉注射免疫球蛋白辅助治疗成人获得性免疫功能低下合并感染的疗效观察

目的观察静脉注射免疫球蛋白(IVIG)辅助治疗成人获得性免疫功能低下合并感染的疗效。方法50例病人随机分组进入本项前瞻性研究,IVIG治疗组和对照组均为25例病人,两组病人的性别、年龄、体重、粒细胞缺乏持续时间和疾病构成等参数相似。IVIG以400mg/kg每天给予,连续5天。观察发热持续时间、抗生素使用时间和感染相关死亡率。结果IVIG治疗组的发热持续时间和抗生素使用时间分别为(15.96±2.88)d和(21.56±6.98)d,对照组为(13.72±5.88)d和(18.60±8.10)d,IVIG治疗组和对照组感染相关死亡率分别为8.0%和8.0%。比较两组发热持续时间、抗生素使用时间和二级疗效均无显著统计学意义(P>0.05)。结论静脉注射免疫球蛋白对成人获得性免疫功能低下合并感染无明显治疗效果。     

Interferon Alfa Versus Interferon Alfa Plus Cytarabine Combination Therapy for Chronic Myeloid Leukemia: A Meta-Analysis of Randomized Controlled Trials

Objective

This article compares the effect of interferon alfa plus cytarabine (IFN-alfa + Ara-C) versus IFN-alfa alone on the chronic phase of chronic myelogenous leukemia.

Methods

Electronic searches were performed in the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese Biomedical Database, China Journal Full-text Database, and Chinese Scientific Journals Database. The languages were limited to Chinese and English. Randomized controlled trials were selected by 2 investigators. Analyses were performed using RevMan 5.0 software.

Results

A total of 3139 patients in 4 studies met the inclusion criteria. In those patients, complete hematologic response and cytogenetic responses showed significant improvements in favor of IFN-alfa + Ara-C, with complete hematologic response relative risk (RR) of 1.15 (95% CI, 1.09–1.21), complete cytogenetic response RR of 1.87 (95% CI, 1.47–2.38), partial cytogenetic response RR of 1.48 (95% CI, 1.25–1.75), and major cytogenetic response RR of 1.61 (95% CI, 1.42–1.83), respectively. The overall 3-year survival rate in the IFN-alfa + Ara-C group was 86% compared with 79% in the IFN-alfa group (RR = 1.09; 95% CI, 1.03–1.14). In the other 2 studies, 5-year overall survival was 69% compared with 63%, respectively (RR = 1.08; 95% CI, 1.01–1.15). However, IFN-alfa and Ara-C involved higher risk of hematologic toxicity, gastrointestinal adverse events, and severe mucositis compared with IFN-alfa monotherapy (RR = 2.63 [95% CI, 1.94–3.56); RR = 3.38 [95% CI, 2.28–5.00], and RR = 8.84 [95% CI, 3.82–20.46], respectively). Weight loss and skin rash were also observed more frequently in the combination treatment group (RR = 2.00 [95% CI, 1.47–2.73) and RR = 3.75 [95% CI, 2.13–6.59], respectively).

Conclusions

In patients with chronic myelogenous leukemia in the chronic phase, the combination of IFN-alfa + Ara-C demonstrated improved complete hematologic response, superior cytogenetic responses, and higher rates of 3- and 5-year survival than IFN-alfa alone. However, combination therapy is more likely to cause serious adverse effects. Well-designed studies will be required to determine the outcomes and adverse effects of the 2 drugs as treatment for patients with chronic myelogenous leukemia who cannot afford molecularly targeted drugs.     

Differential gene expression profiling of oesophageal squamous cell carcinoma by DNA microarray and bioinformatics analysis

Differential gene expression profiling was carried out on primary tumour tissues and adjacent non-neoplastic tissues from patients with oesophageal squamous cell carcinoma (ESCC). RNA extracted from ESCC tissues and matched normal oesophageal epithelium of four ESCC patients was analysed using whole-genome microarrays. Bioinformatics analysis was also carried out to ascertain which genes and pathways may be important in the carcinogenesis of ESCC. A total of 570 genes were identified that differed significantly in expression: 303 genes were up-regulated and 267 genes were down-regulated in ESCC tissues compared with normal oesophageal epithelium. Gene ontology analysis showed that the primary molecular functions of these genes were related to the extracellular region, collagen and endopeptidase inhibitor activity. Pathway analysis revealed seven pathways or networks highly associated with the differential expression profile. Gene set analysis showed that the POD1_KO_UP gene set was significantly enriched, containing 15 matching genes. Thus, a large number of genes are involved in the carcinogenesis of ESCC and participate in various cell processes and pathways.     

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Increasing evidence indicates that survivin, an inhibitor of apoptosis protein (IAP), is expressed in human cancer cells but is absent from most normal adult tissues. Here, we examined the feasibility of using a survivin promoter (Sur-P) to direct therapeutic expression of a proapoptotic gene specifically in human tumor cells. First, we demonstrated that this promoter was highly active in human tumor cells but not in normal cells. Second, we found that Sur-P activity was upregulated by hypoxia in tumor cells. Third, to further enhance this promoter's activity under hypoxia, we added a hypoxia-responsive element (HRE) from the vascular endothelial growth factor gene promoter in its 5' region, and showed that this combination resulted in a further increase in the level of gene expression in hypoxic tumor cells. Finally, we demonstrated that expression of an autocatalytic reverse caspase-3 gene by this promoter specifically induced apoptotic cell death in human tumor cells but not in normal cells. These findings support the use of promoters Sur-P or chimeric HRE-Sur-P for generating novel vectors for cancer gene therapy.     

Electrophysiological characterization of N-methyl-D-aspartate receptors in rat dorsal root ganglia neurons

In the peripheral nervous system, N-methyl-D-aspartate receptors (NMDAR) expressed on the central and peripheral terminals of primary afferent neurons are involved in nociception. We used single cell imaging of intracellular calcium concentration ([Ca2+]i) and patch clamp techniques to characterize the functional properties of NMDARs on adult rat dorsal root ganglia (DRG) neurons in primary culture and selectively on those innervating the distal colon. In Mg2+-free extracellular solution, rapid perfusion of DRG neurons with 250 microM NMDA and 10 microM glycine caused a significant increase in [Ca2+]i, and elicited inward currents in whole cell patch clamp recordings when the holding potential was -60 mV. Both effects were reversibly inhibited by 200 microM ketamine in a use-dependent manner. The EC50 values for NMDA and glycine were 64 and 1.9 microM with Hill slope coefficients of 1.4 and 1.3, respectively. At negative potentials, extracellular Mg2+ blocked currents in a concentration- and voltage-dependent manner. The IC50 for Mg2+ at a holding potential of -100 mV was 2.0 microM. The NMDAR subtype-selective antagonist, ifenprodil, inhibited 94% of the NMDA and glycine-induced current with an IC50 of 2.6 microM. There was no evidence of multiple binding sites for ifenprodil. There was no significant difference in the NMDAR current density on DRG neurons that had innervated the colon, nor was there a difference in the EC50 for ifenprodil. These results demonstrate that functional NMDARs expressed by DRG neurons innervating both somatic and visceral tissues of adult rats are composed predominantly of NR2B subunits.     

Variants of Interleukin-7/Interleukin-7 Receptor Alpha are Associated with Both Neuromyelitis Optica and Multiple Sclerosis Among Chinese Han Population in Southeastern China

Background:

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are autoimmune demyelinating diseases of the central nerve system. Interleukin-7 (IL-7) and interleukin-7 receptor alpha (IL-7Rα) were proved to be important in the pathogenesis of both diseases because of the roles they played in the differentiations of autoimmune lymphocytes. The variants of both genes had been identified to be associated with MS susceptibility in Caucasian, Japanese and Korean populations. However, the association of these variants with NMO and MS has not been well studied in Chinese Southeastern Han population. Here, we aimed to evaluate the association of six IL-7 variants (rs1520333, rs1545298, rs4739140, rs6993386, rs7816065, and rs2887502) and one variant of IL-7RA (rs6897932) with NMO and MS among Chinese Han population in southeastern China.

Methods:

Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MassARRAY system) and Sanger sequencing were used to determine the variants of IL-7 and IL-7RA in 167 NMO patients, 159 MS patients and 479 healthy controls among Chinese Han population in southeastern China. Samples were excluded if the genotyping success rate <90%.

Results:

Statistical differences were observed in the genotypes of IL-7 rs1520333 in MS patients and IL-7RA rs6897932 in NMO patients, compared with healthy controls (P = 0.035 and 0.034, respectively). There was a statistically significant difference in the genotypes of IL-7 rs2887502 between MS and NMO patients (P = 0.014). And there were statistically significant differences in the rs6897932 genotypes (P = 0.004) and alleles (P = 0.042) between NMO-IgG positive patients and healthy controls.

Conclusions:

The study suggested that among Chinese Han population in southeastern China, the variant of IL-7RA (rs6897932) was associated with NMO especially NMO-IgG positive patients while the variant of IL-7 (rs1520333) with MS patients. And the genotypic differences of IL-7 rs2887502 between MS and NMO indicated the different genetic backgrounds of these two diseases.     

Effect of Intravenous Administration of Liposomal Prostaglandin E1 on Microcirculation in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Intervention

Background:

Several studies have demonstrated that primary percutaneous coronary intervention (PCI) can result in reperfusion injury. This study aims to investigate the effectiveness of liposomal prostaglandin E1 (Lipo-PGE1, Alprostadil, Beijing Tide Pharmaceutical Co., Ltd.) for enhancing microcirculation in reperfusion injury. In addition, this study determined the optimal administration method for acute ST elevation myocardial infarction (STEMI) patients undergoing primary PCI.

Methods:

Totally, 68 patients with STEMI were randomly assigned to two groups: intravenous administration of Lipo-PGE1 (Group A), and no Lipo-PGE1 administration (Group B). The corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC) and myocardial blush grade (MBG) were calculated. Patients were followed up for 6 months. Major adverse cardiac events (MACE) were also measured.

Results:

There was no significant difference in the baseline characteristics between the two groups. The cTFC parameter in Group A was significantly lower than Group B (18.06 ± 2.06 vs. 25.31 ± 2.59, P < 0.01). The ratio of final MBG grade-3 was significantly higher (P < 0.05) in Group A (87.9%) relative to Group B (65.7%). There was no significant difference between the two groups in final TIMI-3 flow and no-reflow. Patients were followed up for 6 months, and the occurrence of MACE in Group A was significantly lower than that in Group B (6.1% vs. 25.9% respectively, P < 0.05).

Conclusions:

Myocardial microcirculation of reperfusion injury in patients with STEMI, after primary PCI, can be improved by administering Lipo-PGE1.     

Short-term Rosuvastatin Treatment for the Prevention of Contrast-induced Acute Kidney Injury in Patients Receiving Moderate or High Volumes of Contrast Media: A Sub-analysis of the TRACK-D Study

Background:

Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI). However, the consistency of these effects on patients administered different volumes of contrast media is unknown.

Methods:

In the TRACK-D trial, 2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care. This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV], 200–300 ml, n = 712) or (high contrast volume [HCV], ≥300 ml, n = 220). The primary outcome was the incidence of CIAKI. The secondary outcome was a composite of death, dialysis/hemofiltration or worsened heart failure at 30 days.

Results:

Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1% vs. 4.4%, P = 0.050) in the overall cohort and in patients with MCV (1.7% vs. 4.5%, P = 0.029), whereas no benefit was observed in patients with HCV (3.4% vs. 3.9%, P = 0.834). The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7% vs. 5.3%, P = 0.049) in the overall cohort, but it was similar between the patients with MCV (2.0% vs. 4.2%, P = 0.081) or HCV (5.1% vs. 8.8%, P = 0.273).

Conclusions:

Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.